The statements in this section merely provide background information related to the present disclosure and may not constitute prior art. Arthropods and their relatives are the most numerous of living organisms and nearly one million described species constitute approximately 70% of all animal species. Of these, about 1% are considered significant pests. These pests attack humans and/or their domestic animals; transmit human, animal, and plant diseases; destroy structures; and compete for available supplies of food and other natural resources. In the United States, there are at least 600 species of such economically significant pests.
In an effort to control the damage done by various pests, there has been widespread use and development of pesticides. Pesticides are generally defined as any substance or chemical designed or formulated to kill or control weeds or animal pests. Pesticides directed against animal pests include, e.g., insecticides, acaricides, helminthicides, molluscicides, and rodenticides, which are designed or formulated to either kill or control, respectively: insects, mites or ticks, worms, mollusks, and rodents. Generally, control is achieved by oral ingestion of stomach poisons, contact with poisons that penetrate through the cuticle, or inspiration of fumigants that penetrate through the respiratory system of the pest. Ancillary chemicals can also be employed in pest control and include attractants and repellants, which influence pest behavior, and chemosterilants, which influence reproduction. The control can practiced to prevent pest infestation or to treat an existing infestation, and the infestation can be of a type that is typically either long-term (e.g., as with lice) or transitory (e.g., as with biting flies).
The widespread use of chemical pesticides has resulted in increasing difficulties in practical pest control. Examples of such difficulties include: genetic selection under chemical pressure of strains of more than 400 arthropod (insect and acarine) pests that are resistant to one or more classes of pesticides and some to every available material; resurgences of pests and outbreaks of secondary pests that result from elimination of natural enemies by the use of broad-spectrum pesticides; adverse human-health effects from injudicious use of highly toxic pesticides; and exponentially increasing costs of developing new pesticides.
One area of particular concern is the protection of domestic animals, such as cattle and other livestock, from parasites. Parasites can be continuous or non-continuous, depending on whether the complete life cycle, or only particular stage(s) of the life cycle, is host-based; and non-continuous parasites can exhibit continually parasitic behavior during a particular life stage.
With respect to the protection of livestock and other domestic animals, significant advances have been made against previously pesticide-resistant species of livestock ectoparasites. For example, horn flies (Haematobia irritans irritans), a non-continuous ectoparasite, have been effectively controlled by the use of ear tags containing either pyrethroid or organophosphorus insecticides, including mixtures of organophosphates such as diazinon (i.e., a pyrimidine organothiophosphate) and chlorpyrifos (i.e., a pyridine organothiophosphate), impregnated in a resin base, from which it can be released. The impregnation can be achieved by contacting the resin base article with an active ingredient composition according to the present invention, but in various preferred embodiments, the active ingredient composition can be present in admixture with the resin base components prior to forming an article therefrom The insecticide mixture is slowly released from the resin base onto the skin (epidermis and/or hair) of the animal and exhibits good contact toxicity results with respect to various pests, including horn flies, stable flies, and ticks. A complete discussion of this technology can be found in commonly-assigned U.S. Pat. No. 5,472,955, the entire disclosure being incorporated herein by reference. An ear tag containing a mixture of diazinon and chlorpyrifos is readily commercially available from Y-Tex Corporation (Cody, Wyo.) and is being marketed under the trademark WARRIOR™.
Recently, another ear tag has been developed by Y-Tex Corporation and is being marketed under the trademark PYTHON®. This ear tag is similar to the WARRIOR™ ear tag in that a synergized insecticide is impregnated into a resin base. However, the PYTHON® ear tag differs primarily from the WARRIOR™ ear tag in that the impregnated insecticide is an enriched S-isomer, synthetic pyrethroid compound, as opposed to an organothiophosphate compound. A synthetic pyrethroid compound is generally defined as a synthetic pesticide that mimics pyrethrin, the original botanical pesticide derived from certain species of chrysanthemum flowers. Examples of pyrethroid compounds include, without limitation, allethrins, resmethrins, permethrins, and fenvalerates. The synthetic pyrethroids have the marked advantages of low to moderate toxicity to humans and domestic animals and high effectiveness at low application rates, often one-tenth of those required for organophosphorus and carbamate insecticides. The PYTHON® ear tag utilizes zeta-cypermethrin (empirical formula: C22H19Cl2NO3) as the insecticide. Zeta-cypermethrin (readily commercially available from FMC Corporation, Philadelphia, Pa.) is a mixture of stereoisomers comprising high concentrations of s-isomers of cypermethrin. The zeta-cypermethrin is then combined with a synergist, such as piperonyl butoxide (empirical formula: C19H30O5), to produce a synergized insecticide. The PYTHON® ear tag exhibits excellent contact toxicity against horn flies (including horn flies with moderate pyrethroid resistance), face flies (Musca autumnalis), lice (Phthiraraptera order), Gulf Coast ticks (Ambylomma maculatum), and spinose ear ticks (Otobius megnini).
Other ear tags effective against certain ectoparasites are also readily commercially available from Y-Tex Corporation and are marketed under the trademarks OPTIMIZER® (containing diazinon and being generally effective against pyrethroid-resistant horn flies, face flies, Gulf Coast ticks, spinose ear ticks, and lice) and GARDSTAR® (containing permethrin and being generally effective against pyrethroid-susceptible horn flies, face flies, Gulf Coast ticks, spinose ear ticks, stable flies, house flies, and lice).
Although the aforementioned insecticidal compositions have aided greatly in the control and treatment of various livestock pests, some ectoparasites, especially horn flies and buffalo flies (Haematobia irritans exigua), are now developing resistance to these organophosphorus- and/or pyrethroid-based insecticidal compositions.
As a result, there is a need to provide new or improved pesticidal compositions of other chemical classes in order to allow alternation (i.e. rotation) of different types of pesticides so as to lessen the resistance, or decrease the rate of development of resistance, of local pest populations to any one of the pesticides included in a rotation program, and thereby provide effective whole-life treatment programs for livestock and other animals. A need for alternative pesticide compositions also arises because of variations in local pest species populations, as by, e.g., introduction of foreign pests, changes due to differing seasons or weather conditions, or by moves to different environments, such as indoor-outdoor habitats, wetland-woodland-field habitats, and geographic region habitats. Each of these factors can result in a given pesticide composition's become less effective as a protectant of the livestock or other treated animal, such that rotation with another pesticide composition would be beneficial.
Thus, recent attention has focused toward pesticide compounds that exhibit effectiveness against ectoparasites that have (or are) developing resistance to these organophosphorus- and/or pyrethroid-based insecticidal compositions. Among the compounds being actively developed are the pesticidal macrolides, which are a class of macrocyclic lactones of the polypropionate-type polyketides. Of particular interest among these compounds are those classified as 16-member macrolides, i.e. having a 16-member macrocyclic lactone ring core. Among these are compounds of the avermectin-milbemycin group, examples of which include the abamectins, ivermectins, and milbemectins.
The currently available active ingredient compositions containing one or more types of such macrolides, e.g., ivermectin, are delivered by whole-animal drenching with a pour-on solution, by injection, or by oral administration in relatively large doses. This is a difficult, time-consuming, and expensive undertaking for even a moderately sized livestock operation. Additionally, orally-administered active compositions are sometimes very difficult to administer to an uncooperative animal, especially cattle, and may not be well tolerated by the animal's digestive system. Further, the orally-administered composition may interfere with the animal's performance (e.g., weight gain or milk production) or may inadvertently poison the animal (e.g., avermectin toxicosis). Also, the pest still has to bite the animal in order to receive a toxic dose of an injected or orally administered formulation. Finally, the enteral, parenteral, and topical drenching routes of administration induce a much higher concentration of pesticide in the animal tissues, resulting in the need to comply with a mandatory livestock animal withdrawal period before slaughter, in order to permit metabolic degradation and secretion of the pesticide. Thus, it would be advantageous for all these reasons to provide a pesticidal macrolide formulation that is pesticidally effective, and that can be administered in a less invasive or less pervasive manner, such as with an ear tag. Yet, pesticidal macrolides have been found to exhibit too low a level of pesticidal contact activity to permit ear tag and other point-of-contact applications to be feasible.
Therefore, there exists a need for a safe, effective, ready-to-use, pesticidal macrolide active ingredient composition and method of use thereof for the long-term prevention and treatment of pest/parasite infestation in domestic animals, especially cattle and other livestock, wherein the pesticide composition can be easily incorporated into topical preparations and ear tags and which is effective against horn flies, buffalo flies and other ectoparasites, especially those that have developed (or are developing) resistance to organophosphate- and/or pyrethroid-based insecticidal compositions.